PubMed Health⌕ Search

Biomedical subjects

S D Vernon

Publications and source records attributed to S D Vernon.

26 records · Page 2Linked to original sources
PubMed1995

Human papillomavirus and disease-free survival in FIGO stage Ib cervical cancer.

To determine if human papillomavirus (HPV) in the primary tumor was associated with disease-free survival of stage Ib cervical cancer patients, archival tissues from 47 patients were analyzed for HPV DNA by in situ hybridization (ISH) and polymerase chain reaction. HPV integration was determined by ISH signal pattern. Laboratory data were correlated with clinical parameters and disease-free survival. Kaplan-Meier estimates of 4-year disease-free survival were 56% in women with HPV detected in the primary tumor by ISH and 100% for women in whom HPV was not detected (P = .02). Four-year disease-free survival was 39% for patients with integrated HPV in the primary tumor (P = .005 vs. HPV-negative tumors and .05 vs. HPV episomal or episomal/integrated). HPV detection and integration state was not associated with any other clinical variable. Detection of integrated HPV DNA in the primary tumor was strongly associated with treatment failure.

Adult↗
PubMed1994

Cellular proteins involved in papillomavirus-induced transformation.

Human papillomaviruses (HPVs) are associated with at least 80% of cervical carcinomas and are classified as high-risk or low-risk based on whether or not they are commonly found in cervical cancers. The high-risk HPVs have early gene products (E6 and E7) that immortalize human keratinocytes and are at least partially responsible for causing cervical carcinoma. E6 and E7 from the high-risk viruses interact strongly with the tumor suppressors p53 and Rb; those from the low-risk HPVs do not. Transformation involves a multi-step process and requires additional factors besides high-risk HPV infection. High-risk HPVs are capable of immortalizing primary human keratinocytes in tissue culture, but such cells become transformed only after certain chromosomal changes take place, possibly having to do with oncogene activation. The DNA of high-risk HPVs is frequently (if not always) integrated into the genome of cancer cells; it is normally episomal in premalignant lesions. Integration disrupts the E2 and E5 genes and viral gene regulation. Cells containing integrated viral DNA show excessively high levels of E6 and E7. While there is some conflicting evidence, it appears that the p53 and Rb tumor-suppressor genes are more frequently mutated in HPV-negative tumors than they are in HPV-positive tumors, suggesting that for tumor formation to proceed the p53 and Rb proteins must be inactivated either by interaction with the viral proteins or by mutation. The presence of an activated oncogene in a cell lacking functional p53 or Rb may then be sufficient to cause tumor progression.

Base Sequence↗
PubMed1994

A longitudinal study of human papillomavirus DNA detection in human immunodeficiency virus type 1-seropositive and -seronegative women.

Cericovaginal lavage samples from 124 human immunodeficiency virus type 1 (HIV-1)-seropositive and 126 HIV-1-seronegative women were collected monthly for 8 months and tested for human papillomavirus (HPV) DNA. The estimated prevalence of HPV was 42.8% in HIV-1-seropositive and 13.4% in -seronegative women (P < .001). There was no significant difference in HPV DNA detection in HIV-1-seropositive women with CD4 cell counts of < 300/mm3 (50% HPV-positive), 300-499/mm3 (36.4% HPV-positive), or > or = to 500/mm3 (40.5% HIV-positive). However, HIV-1-seropositive women who were more immunocompromised, as indicated by lower CD4 cell counts, were more likely to shed HPV persistently. The quantity of HPV DNA detected in cervicovaginal lavage samples was similar in HIV-1-seropositive and -seronegative women. This study further defined the characteristics of HPV infections in HIV-1-infected women.

Cervix Uteri↗
PubMed1993

The HIV-1 tat protein enhances E2-dependent human papillomavirus 16 transcription.

Epidemiologic studies show an association between infection with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV) associated anogenital disease. To investigate possible molecular mechanisms of HIV-1 modulation of HPV expression, we studied the effect of an HIV-1 regulatory protein, tat1, on gene expression directed by the upstream regulatory region (URR) of HPV type 16 (HPV 16). HPV 16 URR-directed chloramphenicol acetyltransferase (CAT) expression driven by the native HPV 16 promoter (P97) was increased in the presence of tat1 alone. Tat1 also reversed E2-mediated repression of P97-directed CAT expression. E2 mediated CAT expression with URR constructs containing the SV40 promoter was enhanced when tat1 and E2 were cotransfected. Using a cervical carcinoma cell line (SiHa), E2 enhancement of URR-directed gene expression was elevated in the presence of extracellular tat1 or during cocultivation with HIV-1-infected cells. These results show HIV can modulate HPV gene expression in cell culture and that the increased rate of HPV-associated cervical disease in asymptomatic HIV-seropositive women may result from HPV-HIV molecular interactions.

AIDS-Related Opportunistic Infections↗
PubMed1992

Human papillomavirus, human immunodeficiency virus, and cervical cancer: newly recognized associations?

There are now sufficient data to conclude that women infected with human immunodeficiency virus (HIV) have an increased risk of human papillomavirus (HPV) infection and preinvasive stages of cervical cancer. This association is not completely due to immunosuppression. It is likely that HPV pathogenesis is altered in HIV-infected women. Preinvasive cervical neoplasia likely occurs more frequently in HIV-infected women because of several factors, including immunosuppression, viral interactions, and alterations in viral pathogenesis. As new treatments prolong the life of HIV-infected individuals, we must continue to be aware of and reactive to an increasing number of opportunistic complications of HIV infection, such as HPV infection and associated diseases.

AIDS-Related Opportunistic Infections↗
PubMed1990

Vesicular stomatitis New Jersey virus glycoprotein gene sequence and neutralizing epitope stability in an enzootic focus.

Vesicular stomatitis New Jersey (VS NJ) virus is capable of undergoing rapid evolution in nature and therefore has the potential for antigenic variation. We selected an area of Costa Rica where VS NJ virus is enzootic to study whether this virus used the mechanism of antigenic variation to persist in nature. Three sentinel herds and three nonsentinel herds were observed from 1986 to 1988. Eleven VS NJ virus isolates were collected from naturally infected cattle. Remarkably, nine animals that were bled prior to reinfection with VS NJ virus had neutralizing antibody titers up to 1: 102,400 yet virus was isolated from, and disease was observed in, these animals. Sequence analysis of the portion of the glycoprotein gene coding for the neutralizing epitopes demonstrated that all virus isolates were 98-100% similar with no indication of specific genetic variation. The 3' end of the glycoprotein gene also remained stable in that all isolates were again 98-100% similar in nucleotide sequence. Each isolate was neutralized to equivalent titers with monoclonal antibodies directed against four neutralizing epitopes on the glycoprotein. Additionally, preisolation sera from each animal were able to neutralize the virus that caused the subsequent disease. These results provide evidence that antigenic variation is not a mechanism used by VS NJ virus to persist in an enzootic focus of Costa Rica.

Animals↗
PubMed1985

Recent vesicular stomatitis virus infection detected by immunoglobulin M antibody capture enzyme-linked immunosorbent assay.

We developed an enzyme-linked immunosorbent assay (ELISA) that was capable of detecting immunoglobulin M (IgM) antibody to vesicular stomatitis virus (VSV) in the sera of experimentally and naturally infected cattle and horses. The detection of IgM in the sera of these animals permitted an estimate of the recency of infection by VSV serotype New Jersey. A VSV serotype New Jersey epizootic strain isolated from a horse and passed once in an Aedes albopictus cell line was used to infect a horse and a calf. Sera from these animals were used to standardize the ELISA. This assay was used to test sera from cattle and horses involved in the 1982 VSV epizootic. Comparative antibody titrations were performed by three systems: the serum-dilution plaque-reduction neutralization, complement fixation, and indirect immunofluorescent tests. The antibody titers by neutralization and the ELISA were comparable for the period that IgM was present; when IgM ELISA titers diminished, the neutralization titers remained high. The complement fixation and indirect immunofluorescent antibody titers followed closely the IgM pattern determined by the ELISA. The capture IgM ELISA is applicable for the rapid detection of IgM antibody to VSV in cattle and horses and is a useful assay of recent infection.

Animals↗